MPAS_CLAUC
ID MPAS_CLAUC Reviewed; 2545 AA.
AC A0A0R8YWJ7;
DT 02-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT 11-MAY-2016, sequence version 2.
DT 03-AUG-2022, entry version 23.
DE RecName: Full=Methylphloroacetophenone synthase {ECO:0000303|PubMed:26895859};
DE Short=MPAS {ECO:0000303|PubMed:26895859};
DE EC=2.3.1.- {ECO:0000305};
DE AltName: Full=Non-reducing polyketide synthase MPAS {ECO:0000303|PubMed:26895859};
DE AltName: Full=Usnic acid biosynthesis protein MPAS {ECO:0000305};
GN Name=mpas {ECO:0000303|Ref.2};
OS Cladonia uncialis (Cup lichen).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Lecanoromycetes;
OC OSLEUM clade; Lecanoromycetidae; Lecanorales; Lecanorineae; Cladoniaceae;
OC Cladonia.
OX NCBI_TaxID=174080;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND INDUCTION.
RX PubMed=26895859; DOI=10.1016/j.funbio.2015.10.009;
RA Abdel-Hameed M.D., Bertrand R.L., Piercey-Normore M.D., Sorensen J.L.;
RT "Putative identification of the usnic acid biosynthetic gene cluster by de
RT novo whole-genome sequencing of a lichen-forming fungus.";
RL Fungal Biol. 120:306-316(2016).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Wen L., He K., Yang H.;
RL Submitted (FEB-2016) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP REVIEW ON BIOTECHNOLOGY.
RX PubMed=25707417; DOI=10.1080/14786419.2015.1007455;
RA Araujo A.A., de Melo M.G., Rabelo T.K., Nunes P.S., Santos S.L.,
RA Serafini M.R., Santos M.R., Quintans-Junior L.J., Gelain D.P.;
RT "Review of the biological properties and toxicity of usnic acid.";
RL Nat. Prod. Res. 29:2167-2180(2015).
CC -!- FUNCTION: Methylphloroacetophenone synthase; part of the gene cluster
CC that mediates the biosynthesis of usnic acid, a dibenzofuran lichen
CC product possessing a broad spectrum of biological activities
CC (PubMed:26895859). Two genes, mpas and mpao, comprise the usnic acid
CC biosynthetic gene cluster with a single post-PKS enzyme, the
CC methylphloracetophenone oxidase (mpao) (PubMed:26895859). The
CC methylphloroacetophenone synthase (mpas) is a non-reducing polyketide
CC synthase that produces methylphloracetophenone from acetate via a
CC methylated tetraketide intermediate (PubMed:26895859). The
CC methylphloroacetophenone oxidase then carries out the oxidative
CC dimerization of methylphloracetophenone to usnic acid
CC (PubMed:26895859). {ECO:0000269|PubMed:26895859}.
CC -!- INDUCTION: Expression is lower in the cultured mycobiont when compared
CC to the wild-type lichen (PubMed:26895859).
CC {ECO:0000269|PubMed:26895859}.
CC -!- DOMAIN: The formation of methylphloracetophenone leading to
CC dibenzufurans such as usnic acid requires a 1,6-Claisen-style
CC condensation performed by a terminal CLC domain that simultaneously
CC aromatizes the tetraketide and releases it from the PKS
CC (PubMed:26895859). {ECO:0000269|PubMed:26895859}.
CC -!- BIOTECHNOLOGY: Lichens belonging to usnic acid-containing genera have
CC been used as crude drugs throughout the world (PubMed:25707417). Usnic
CC acid is a potentially interesting candidate for such activities as
CC anti-inflammatory, analgesic, healing, antioxidant, antimicrobial,
CC antiprotozoal, antiviral, larvicidal and UV protection
CC (PubMed:25707417). However, it was shown to be toxic for the liver and
CC to lead to contact allergy (PubMed:25707417).
CC {ECO:0000269|PubMed:25707417}.
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DR EMBL; KT363732; ALA62323.2; -; Genomic_DNA.
DR AlphaFoldDB; A0A0R8YWJ7; -.
DR SMR; A0A0R8YWJ7; -.
DR GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IEA:InterPro.
DR GO; GO:0016787; F:hydrolase activity; IEA:InterPro.
DR GO; GO:0008168; F:methyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:InterPro.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IEA:UniProt.
DR Gene3D; 1.10.1200.10; -; 1.
DR Gene3D; 3.10.129.110; -; 1.
DR Gene3D; 3.40.366.10; -; 2.
DR Gene3D; 3.40.47.10; -; 1.
DR Gene3D; 3.40.50.150; -; 1.
DR Gene3D; 3.40.50.1820; -; 1.
DR InterPro; IPR029058; AB_hydrolase.
DR InterPro; IPR013094; AB_hydrolase_3.
DR InterPro; IPR001227; Ac_transferase_dom_sf.
DR InterPro; IPR036736; ACP-like_sf.
DR InterPro; IPR014043; Acyl_transferase.
DR InterPro; IPR016035; Acyl_Trfase/lysoPLipase.
DR InterPro; IPR041068; HTH_51.
DR InterPro; IPR018201; Ketoacyl_synth_AS.
DR InterPro; IPR014031; Ketoacyl_synth_C.
DR InterPro; IPR014030; Ketoacyl_synth_N.
DR InterPro; IPR013217; Methyltransf_12.
DR InterPro; IPR020841; PKS_Beta-ketoAc_synthase_dom.
DR InterPro; IPR020807; PKS_dehydratase.
DR InterPro; IPR042104; PKS_dehydratase_sf.
DR InterPro; IPR020806; PKS_PP-bd.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR InterPro; IPR032088; SAT.
DR InterPro; IPR016039; Thiolase-like.
DR Pfam; PF07859; Abhydrolase_3; 1.
DR Pfam; PF00698; Acyl_transf_1; 1.
DR Pfam; PF18558; HTH_51; 1.
DR Pfam; PF00109; ketoacyl-synt; 1.
DR Pfam; PF02801; Ketoacyl-synt_C; 1.
DR Pfam; PF08242; Methyltransf_12; 1.
DR Pfam; PF00550; PP-binding; 1.
DR Pfam; PF14765; PS-DH; 1.
DR Pfam; PF16073; SAT; 1.
DR SMART; SM00827; PKS_AT; 1.
DR SMART; SM00825; PKS_KS; 1.
DR SMART; SM00823; PKS_PP; 1.
DR SUPFAM; SSF47336; SSF47336; 1.
DR SUPFAM; SSF52151; SSF52151; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR SUPFAM; SSF53474; SSF53474; 1.
DR SUPFAM; SSF53901; SSF53901; 1.
DR PROSITE; PS00606; B_KETOACYL_SYNTHASE; 1.
DR PROSITE; PS50075; CARRIER; 1.
PE 1: Evidence at protein level;
KW Acyltransferase; Methyltransferase; Multifunctional enzyme;
KW Phosphopantetheine; Phosphoprotein; Transferase.
FT CHAIN 1..2545
FT /note="Methylphloroacetophenone synthase"
FT /id="PRO_0000437583"
FT DOMAIN 1657..1731
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 8..261
FT /note="N-terminal acylcarrier protein transacylase (SAT)
FT domain"
FT /evidence="ECO:0000255"
FT REGION 386..801
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255"
FT REGION 914..1218
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255"
FT REGION 1296..1604
FT /note="Product template (PT) domain"
FT /evidence="ECO:0000255"
FT REGION 1748..1773
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1931..2163
FT /note="Methyltransferase (CMeT) domain"
FT /evidence="ECO:0000255"
FT REGION 2198..2544
FT /note="Claisen cyclase (CLC) domain"
FT /evidence="ECO:0000305|PubMed:26895859"
FT ACT_SITE 547
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 1001
FT /note="For acyl/malonyl transferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 2321
FT /note="For thioesterase activity"
FT /evidence="ECO:0000250|UniProtKB:Q5ATJ7"
FT ACT_SITE 2481
FT /note="For thioesterase activity"
FT /evidence="ECO:0000250|UniProtKB:Q5ATJ7"
FT ACT_SITE 2513
FT /note="For thioesterase activity"
FT /evidence="ECO:0000250|UniProtKB:Q5ATJ7"
FT MOD_RES 1691
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 2545 AA; 278261 MW; 07DA6C76D3A677E1 CRC64;
MALPSLIAFG ALAPWPASDR LDQLRNALQH HNSLKPITKA IQELPLLWKA LSNQDQSLHS
IAGEAAADQL AQWISGAGTA QLVDDKGNVT RMPLTTIAQI AQYVSYLCQY EEPLRHESII
KSAAIGGGIQ GFCIGLLSAL AVASGKTEDD VGNFAAMSVR LAFCVGAYVD LDRHRNGGDS
KASTIAVRWK TPTTLEDIQR LLSRHPDTYI AVVRDIRDVT ITVPASVMEH LIEDLSQIGA
SLRDTGVSGR YHVAIHEGIP QKILETCQAQ FSPTINGQPL VRSNTDAHLF SGEDTALLAL
ECILGERADW YSTISTAASA LNQISANPFI LSIGTDPVPQ SVARSFPVVK ATMIADRVNG
IVEPEIPALA PDPFGSVSQG YPKDAIAIIG MGCRFPGADS IDEYWNLLTE GKSMLSEIPE
ARFGRGRPAR SNSSLRFWGN FLRDIEAFDH GFFKKSPREA VSMDPQQRVL LQVAYEALES
SGYFADSSRP EDVGCYIGAC ATDYDFNVAS HPPSAYSAIG TLRSFLSGKL SHYFGWSGPS
LVLDTACSSS AVAIHTACTA LRTGQCSQAL AGGITLMTSP YLYENFAAAH FLSPTGSSKP
FSADADGYCR GEGGGLVVLK RLSDALRDND HILGVIAGSA VNQNDNCVPI TVPHTSSQGN
LYERVTEQAG VRPSEVTFVE AHGTGTPVGD PIEMESIRRV FGGLHRVAPL IVSSAKGNIG
HLEGASGVAA LIKALLQMEH HLAPRQASFK TLNPKIPALE PDNLCIPTSN LALSGERLAA
CINNYGAAGS NAAMIVLEPP RKSVTYHDKS KMSISSRPKI HPIQLAAASL GGLLAYCVAL
DQYCQRLRFT QDTSEQPQVL SDLAYSLSTR LNQELPFTLT MTVTDLDQLQ AQLRQQTVTS
NNIKQRSKAP PVVLCFGGQV SDRVALDKCL WQESTLLRSY LDICDNTLRV LGYPGLYPSI
FQNEAVTDVV LLHSMIFALQ YSCAQAWLES GLKVDALVGH SFGQLTALCV SGILSLRDGL
RLVAGRASLM QKHWGPESGK MIAIETDQQT LEELQKVICE SNASYNFEIA CFNGPTSHVV
VSDRCSASEL ETKLMERAIR HRSLDVPYGF HSRFTEPLLP HLEDLASSLT FHEPKIPLET
CTDMGTWTEP TSKLIAAHTR EPVFFGKAIQ RLQARLGPCT WLEAGSDSSI VNMVRRALGQ
ASATANNFVS LQLNKPNSSK LVVDATVALW DASHRAQFWN FHRLQRRQYD HLRLPPYAWE
KSKHWLELDM SAALNSDKTN TPPPTNTAAQ VELPAVLIRL KSFDSQGHHF VINPSSEEYQ
TIVKDLESLG SAVCPSTLYV ELASRAVRVA EEDKGNGLLS IKDLRVHSLL GVNVHQTISL
DLQRLAQSWR FRITNADGSI SGSNPGESFC HAEGTVNLKV ADDSLEEEFC RYERLTGHNK
IISIADDPRS ESLRGNVLYN MLGRVVNYPD WYRGVKSVAA LDLRVVAKVT CPVGIPEIVS
KESTTQLPIL ESFIQIASLH ANCLHECRGG EVFQFTRADH MQWAPGFDLH GYGDSAEASW
DVLAYNSTNA ENVVYDIFVH DAVTGRLVLL VLGANFTDIR RPVPISAGLN TSLASEKDIP
MLKNANAERA EISLNSQLPA ESHSQANLTR PGKDAKTSIY EDICGLLEKL ADIPGDQVSG
EATFDNLGVD SLMMIEVISE LSTLFRVDLP IHELEELTDI NSLVDYLHGK GCVGSLYVED
SGNASSLSSS HAISTGASSP PDSSGASAMT TPPETLSLVD YPGSLTTKQE SRAAPAISNG
TGRQPLDMGP YGIQQVFTRL RFDFEKYAEQ TGAKGFWTNV YPQQADLVCA YVVDAYRKLG
CDLATLAAGQ QLPSMNTLPR HKHLVAQLRN ILVESGLLEL RGNQVHVRTA KTVDSTPTAI
RYEQMLQRHP FGASETKLLN VTGPRLADCL TGQKEPLSLL FGDKHNRDLL ADFYANSQML
KAATRLLAEF VSSTFSAAQS GDTLCILEVG AGTGGTTRYL VDVLNRCGIP YEYTFTDISQ
SLVTQAKRNF ASLPQMRFMT FDCDRPAPQE LLGKFHIVIS TNCIHATSNI TTSTTNILPT
LRDDGVLCLV EFTRNLYWFD LVFGLLEGWW LFSDGRQHAL ANEWFWDRSL RAAGFKHVSW
TDGNTEEAKT LRLICAFRGE AKEDRNLAAP NGAITKRAGV PMEEVVWKRV GTLDLSADIY
FPKTPDPPGK KRPIALLIHG GGHFLFGRKD VPMKHIRTLI ERGFLPISTD YRLCPETNLF
EGPMTDCCDA LKWATETLPT LPLSGPTVRP DPTKVVSLGW SSGGQLAMSL GYTAPVKGIK
APDAIFALYP PSDMESNHWH QPCYPLAAEE EPTEILDILA GVRESPIVEY APVSEKRTMA
LSLTLKDDRA SIILHMCWKS QTVPILVHGL PYKKNLPDTD KTDWKYRPPA SAEQVQAISP
LWQIRQGNYK TPTFIVHGNG DDWLPLSMSE RTVEELKRRG IPASLAVPEQ CGHAFDLFPV
GDPLGVGWTS LEQGYDFICR QLGMS
